2. Hemostasis and Blood Coagulation Flashcards
Coagulation and Dentistry • Tooth Extraction-Up to 10% of extraction wounds heal improperly: • Further complicated by: – Poor general health (\_\_\_\_, Vitamin C and \_\_\_\_ deficiency) – Compromised \_\_\_\_ Function – Genetic \_\_\_\_ Disorders – Patients on Anti-\_\_\_\_
* Blood coagulation depends on Vit K, C and folate deficiency - complicate extractions and contribute to bleeding disorders * Alcoholics, individuals on medications, hepatitis patients, HIV/AIDs, fasting, albumin-issues, potent chemotherapies - compromised liver function
vitamin K folate liver hemorrhagic coagulants
• Hemostasis- a series of regulated processes that maintain blood
in a ____, ____STATE in normal vessel while rapidly forming a ____ PLUG, at the site of vascular injury.
* Series of processes that allow blood to be fluid and clot-free when there is no injury - mostly anti-coagulants/anti-aggretory * However, when site of injury > very quickly need to form localized hemostatic plug (liquid into a solid structure) > involves a series of pro-coag/pro-agg compounds * When balance shifts > various problems > hemostasis goes awry
fluid
clot-free
localized hemostatic
When hemostasis goes awry
• Hemorrhagic disorders- characterized by excessive bleeding, hemostatic mechanisms are either ____ or insufficient to prevent normal blood loss.
• ____ disorders- blood clots (thrombi) that are formed within intact blood vessels or within chambers of the heart- discuss in more detail in Thrombosis-Embolism.
• Pro-aggretory mechanisms here are inhibited - hemorrhagic disorders • Thrombotic - not necessarily at a site of \_\_\_\_, obstruct vasculature, leading to complications ○ Increase in pro-aggretatory vs. anti > thrombus formation
blunted
thrombotic
injury
Normal Clotting In Response to Injury
Relies on complex interaction between all three components:
- ____- Endothelium and underlying ECM.
- ____
- ____ Cascade• Platelets form the ____
vascular wall
platelets
coagulation
platelet plug
Coagulation is initiated by…..
• ____ to the vascular wall and surrounding tissue.
• Contact of blood with damaged ____
Stages of Hemostasis
• Vasoconstriction (____ phase)- Transient
• Platelet Activation Phase-Formation of a ____
• Coagulation Phase – coagulation phase activation, ____ and ____ formation.
• Fibrinolytic Phase: Clot ____ and ____
• This process occurs in four distinct stages… • Do not want to vasoconstrict for a period of time • Platelet plug is stabliized via fibrin mesh and clot - utilizes a coagulation cascade ○ Coagulation is \_\_\_\_ phase, platelet activation is \_\_\_\_
trauma
endothelium
vascular platelet plug fibrin mesh clot stabilization resorption
second
primary
Vascular Phase: Vasoconstriction
• Contraction results from
– ____ reflexes- by pain nerve impulses
– ____-
contraction of blood vessels- vascular spasm
– Local humoral factors- platelet release of vasoconstrictor ____
• Vasoconstriction- reduces flow of blood from vessel rupture
* Locally - TXA2, and \_\_\_\_ results in vasoconstriction * Recruit \_\_\_\_ to that site of injury
nervous local myogenic spasm TXA2 endothelin platelets
First responders - platelets
Auto-catalytic
Resting platelet:
• Small (1-4 micrometers in diameter), ____, circulating, smooth discs derived from ____,
• Normal concentration in blood is ____ mg/dL
• Half-life in blood ____ days.
Activated platelet:
Adhere to ____ and ECM (collagen, fibronectin, proteoglycans) and change ____
Activation-Secrete ____ containing pro- coagulants
Aggregate to form a platelet plug and provide catalytic surface
* Von willibron factor - protein that is utilized during \_\_\_\_ * These processes happen \_\_\_\_, and it's \_\_\_\_
anuclear
megakaryocyte
150,000-450,000
8-12
vWF
shape
granules
adherence
simultaneously
auto-catalytic
- Injury
- Adhesion:
➢____
➢-Collagen - Activation:
➢____ Changes
➢Granule Secretion ➢____ loops
4. Aggregation: ➢\_\_\_\_ ➢Thrombin production ➢\_\_\_\_
• Thrombin cleaves \_\_\_\_ into fibrin - going from a mechanical plug, to a more \_\_\_\_ mesh that has fibrin holding it down
von willebrand factor (vWF) membrane feedback vWF fibrinogen
fibrinogen
organized
Adhesion- process by which platelets adhere to damaged regions of vessels
• Interaction between platelet Surface receptor (____) and ____. Platelet GpIIb-IIIa- bind ____
• Interaction between platelet receptor and exposed collagen
– vWF stabilizes interaction with collagen against ____ of blood flow
– vWF acts as ____ for platelets followed by adherence of platelets to ECM
• vWF binds to specific integrin on platelet (\_\_\_\_) > in presence of ADP > platelets expose second integrin (\_\_\_\_), which is a receptor for fibrinogen • 3 common deficiencies in these factors - deficiency in vWF ○ Not able to catch \_\_\_\_ - you're going to have increased bleeding ○ Deficiency in \_\_\_\_ (Glosmon etc. etc.) § Increased bleeding ○ Deficiency in integrin that is binding \_\_\_\_ (Bernand-Solar?) § Increased bleeding ○ Deficiency in \_\_\_\_ is most common
GpIb vWF fibrinogen shear forces catcher
GpIb GpIIb-IIIa catching integrin vWF vWF
Platelet Activation- process by which platelets respond to binding ECM
Results in
➢ Shape change- ____ spiny spheres.
➢ Formation of activated surface
➢ Secretion of granules in response to activation.
➢ Granules (____ and ____-granules) contain
– ____, ATP, ____, calcium
– ____ factors
– ____ factors
• Inactive state - platelets contain granules - dense and alpha • As they begin to adhere and activated, they secrete the contents of their granules ○ ADP - potent \_\_\_\_ agent - beacon to all other platelets ○ TXA2 - \_\_\_\_, minimal ○ \_\_\_\_ - coaggulation cofactors ○ GF - reform the \_\_\_\_
sticky dense alpha ADP TXA2 coagg growth
pro-agg
vasoconstrictor
Ca++
endothelium
Platelet Aggregation- process by which platelet plug is formed prior to fibrin stabilization.
- Sets the process of thrombin processing fibrinogen to ____ in motion
- GpIIb-IIIa on platelets binds ____ forming a bridge between adjacent platelets. Concurrently-there is an activation of thrombin via ____ complex
- Bring the fibrinogen with them, in order to form the fibrin
- Bound to the collagen, and they have spiky “hands” > start pulling in two sides of site of injury to try to organize the area and make a stable clot
- Platelet surface is going to form the surface onto which ____ binds, as the last step in the coagulation cascade
fibrin
fibrinogen
pro-thrombinase
pro-thrombin
Primary Hemostasis-Formation of a platelet plug
• At injury, platelets bind collagen, caught by ____, collagen activates platelets, platelets change shape, release granules, ____ is a potent pro-agg compound, ____ is a mild vasoconstrictor and is pro-agg
• The entire surface is geared to recruit more platelets
• As aggregate, they form a ____ plug
vWF
ADP
TXA2
hemostatic
Aggregation: a delicate balance between Endothelium and platelets
➢ Endothelium produces Anti-aggregatory agents.
➢ ____
➢ ADPase
➢ Platelets secrete- Pro-aggregatory agents.
➢ ____
➢ ADP (at high levels feeds back to stimulate ____)
• You don't want platelets aggregating upstream or downstream of inflammatory - do not want clots here - vessel occlusion • Endothelium itself has anti-agg properties ○ Doesn't have EC collagen exposed ○ Synthesizes prostacyclin - anti-agg compound ○ Synthesizes ADPase - cleaves ADP • Balance of focusing pro-agg at only at site of injury, and the rest of the endothelium maintains its anti-agg properties • The platelets secrete pro-agg ○ TXA2 and ADP
prostacyclin (PGI2)
TXA2
PGI2
Coagulation Cascade
What causes initiation of the coagulation cascade?
____ to the vascular wall and surrounding tissue release of tissue factor.
Contact of blood with damaged ____.
- Basic Principle: each reaction depends on the assembly of an ____ (an activated coagulation factor), a ____ ( a pro-enzyme form of the next coagulation factor in the series) and a ____ ( a reaction accelerator- often ____)
- Assembled on a phospholipid surface either the ____ surface or the ____ surface.
- Release of TF, and contact of blood (contains factors that are activated by TF to form thrombin)
- Phospholipid surface = ____ surface
trauma endothelium enzyme substrate cofactor Ca++
endothelial
platelet
platelet
• Two pathways: Intrinsic (in vitro) and Extrinsic
– ____ delineation
– ____ between two pathways
• Two pathways converge at common factor- ____ to form the prothrombinase complex. End result is production of thrombin which catalyzes cleavage of fibrinogen to ____
• Extrinsic Pathway- Most ____ Relevant
– Begins with trauma to the vascular damage and release of ____ which activates pathway
– Explosive- in severe tissue trauma clotting occurs within ____ seconds
artificial
cross-talk
factor X
fibrin
physiologically
tissue factor
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